Antipsychotics Raise Mortality Risk in Parkinson’s Patients

By staff

Philadelphia—Medications prescribed to Parkinson's disease patients who develop psychosis significantly raise short-term mortality rates, according to a new study that urges the therapy be used only as a last resort.

The study in JAMA Neurology suggests that the antipsychotics often do more harm than good for a subset of patients.

Researchers at the Perelman School of Medicine at the University of Pennsylvania, the University of Michigan Medical School, and the Philadelphia and Ann Arbor Veterans Affairs (VA) Medical Centers analyzed about 15,000 patient records in the VA database to determine that Parkinson’s patients who began using antipsychotic drugs were more than twice as likely to die during the following 6 months, compared to a matched set of Parkinson’s patients who did not use the drugs.

Background information in the articles underscores that the findings are not the first to associate antipsychotic drugs with increased mortality. Since the early 2000s, researchers have linked increased mortality with antipsychotic use among patients who have dementia in the general population, and, since 2005, FDA black box warnings have been required on antipsychotic drug packaging, warning of the increased risk of death when these drugs are used in dementia patients.

While psychosis in Parkinson’s, occurring in about 80% of patients, often is associated with dementia and later-stage disease, “It happens not uncommonly earlier in the course of the illness,” Weintraub said.

For the study, researchers compared a group of 7,877 Parkinson’s patients who were prescribed antipsychotic drugs at any time during 1999-2010 to a similar control group who did not use antipsychotic drugs.

Results indicate that, within the 180 days after they first took antipsychotic drugs, patients in the intervention group had 2.35 times the mortality of the nonusers.

The risk appeared to vary by drug, according to the report, with an increase of 2.16 times for quetiapine fumarate compared with nontreatment, 2.46 for risperidone, 2.79 for olanzapine, and 5.08 for haloperidol. About a 50% greater relative mortality risk was identified with first-generation typical antipsychotics, such as haloperidol, compared to newer atypical antipsychotics such as risperidone and quetiapine, the study notes.

Weintraub suggests that healthcare professionals avoid prescribing antipsychotics to Parkinson’s patients when possible, suggesting they first look at treating comorbid medical conditions associated with psychosis, reducing the dosage of dopamine replacement therapies, and otherwise managing the psychosis without antipsychotics.

“Antipsychotics should be used in these patients only when the psychosis is of clinical significance, and patients probably should not be left on these drugs long-term without re-evaluation,” he said.

In an accompanying commentary, Mark S. Baron, MD, of Virginia Commonwealth University Health System and Hunter Holmes McGuire Veterans Affairs Medical Center, both in Richmond, pointed out the limitations of the study, noting, “Thus, as in other related studies, we are uncertain whether the underlying psychosis or the treatment itself poses the risk for mortality.”